1. Field of the Invention
This invention relates to melt crystallization purification of lactides, including optically active forms thereof, whereby the lactide is substantially completely separated from impurities, including hydroxylic impurities such as water, monomers and oligomeric hydroxycarboxylic acids normally produced along with the lactide during its manufacture, as well as other impurities such as solvents and catalysts. In addition, this invention relates to the separation and purification of lactides existing in more than one isomeric form. Such purification affords the lactides in high and/or controlled states of purity, simply and expeditiously, without the use of selective solvents, fractional crystallization from solvents, distillation or other physical means described in the art.
2. Description of Related Art
Lactide (1,4-dioxane-3,5-dimethyl- 2,5-dione) is an intermediate to high molecular weight polylactic acids disclosed to be useful in biomedical and other applications because of their ability to be degraded biologically and hydrolytically to physiologically and environmentally acceptable by-products.
To achieve the high molecular weights required for such use it is necessary that the lactide be substantially free of hydroxylic (including hydroxycarboxylic) impurities, since such impurities prevent the attainment of desired molecular weights. It is preferred that the acid content of lactide, for example, be less than 10 milliequivalents per kilogram (meq/kg), more preferably less than 5 meq/kg.
Another factor of importance is the stereoisomeric form of the lactide. While lactic acid exists in both a D and L stereoisomeric form, the lactide has in addition a meso form. The racemic mixture of D and L lactides, also of commercial importance, is referred to as the DL lactide. These isomeric lactides have differing stabilities and also give rise to polymers with substantially different properties, making it necessary for some polymer applications to control the ratio of each isomeric form in the final product. These ratios may be controlled either by using processes which make only a single isomer or by purifying a mixture of the isomers. The purification processes in the art are extremely cumbersome and difficult because of the close physical properties of the isomers.
Lactide is most conveniently prepared by polymerizing the corresponding lactic acid to a relatively low molecular weight (oligomeric) polylactic acid, then heating the oligomer, generally in the presence of a catalyst, as is well known in the art, to depolymerize it to the lactide, which is then recovered as a component of a vapor product stream. See Gruter et al, U.S. Pat. No. 1,095,205 (1914); Lowe, U.S. Pat. No. 2,668,162 (1954); Bhatia, U.S. Pat. No. 4,835,293 (1989); DeVries, U.S. Pat. No. 4,797,468 (1989); and Muller, U.S. Pat. No. 5,053,522 (1991), which patents are incorporated herein by reference.
The vapor product stream invariably contains not only the lactide but volatile hydroxylic impurities, among them water, the monomeric lactic acid which is more volatile than the lactide, and often higher boiling oligomers of the lactic acid, all of which are undesirable as they are polymerization chain stoppers which prevent the attainment of desired molecular weights. It may also contain small amounts of solvents or catalysts remaining from previous processing steps. Typically, the vapor product stream contains more than 90% lactides including any isomers and less than 10% impurities.
The typical art procedure for the separation and recovery of the lactide from the vapor product stream generally involves scrubbing with a solvent or crystallization from a solvent. Under such conditions, however, the hydroxylic impurities, particularly water and lactic acid, are capable of undergoing ring-opening reactions with the lactide, resulting in a decrease of lactide yield and an increase of the acidity of the product. The higher the temperature of the recovery process employed, the more likely it is that such reactions will occur.
Moreover, reliance on a solvent, whether for scrubbing the vapor product stream to recover the cyclic ester or for purifying it by recrystallization, is disadvantageous as it necessitates facilities for storing the solvent, using it, purifying it and preventing it from escaping into and contaminating the environment, all of which add significantly to the process investment and operating costs.
An alternate procedure, the purification and recovery of the lactide by distillation and condensation, tends to suffer in that a significant loss of product is often encountered, evidently owing to the reaction of the water and other hydroxylic acid impurities with the lactide at distillation temperatures. Also in the high temperature, acidic environment corrosion of the distillation device can lead to metal ion formation which in turn can catalyze premature lactide polymerization in the equipment itself.
The separation of lactides which are present in more than one isomeric form is even more complex, often involving a combination of multiple solvent recrystallizations and fractional distillations.
Melt crystallization techniques have sometimes been used for purification of certain organic compounds. However, the feasibility of this method cannot be easily predicted. Not only does it depend on the freezing points of the desired product, its impurities and their mixtures with the product, i.e. whether the impurities form a eutectic mixture or a solid solution with the product to be purified, but also on the structure of the crystals formed and therefore their tendency to occlude impurities. Furthermore, the size and productivity of the crystallization equipment depend on the rate at which suitable crystals can be formed without occlusion of the impurities in the crystal structure. As stated in a recent review of this technology (Wynn, "Separate Organics by Melt Crystallization", Chemical Engineering Progress, March 1992, pp 52-60): "Unfortunately, in melt crystallization, the critical steps are rate dependent. They cannot be predicted accurately from theory. Laboratory or pilot-plant data must be generated before even process feasibility can be established."
Further difficulties may arise in cases where the impurities can react with the material to be purified, as is the case with typical impure lactide, making the feasibility of this approach even less predictable.
Thus a need exists for a new and improved solvent-free method of purifying lactides, particularly such lactides contaminated with minor amounts of such hydroxylic impurities as water, monomeric lactic acid and oligomers thereof, which minimizes the disadvantages of prior art methods while simply and expeditiously providing the lactides in high purity suitable for the production of high molecular weight polymers. In addition, a need exists for a solvent-free process for separating isomeric forms of such lactides from its isomers, allowing production of a product with a controlled distribution of isomers.